Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.
Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.
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DOI：
10.1056/nejmoa2201662
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发表时间：
2022-08-18
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预防2019年严重冠状病毒病（Covid-19）的早期治疗是综合应对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行的重要组成部分。在这项双盲、随机、安慰剂对照第 3 阶段试验中，我们采用 2×3 析因设计来测试三种新用途药物（二甲双胍、伊维菌素和氟伏沙明）在预防非住院成人严重 SARS-CoV-2 感染方面的有效性，这些成人在确诊感染后 3 天内和症状出现后 7 天内入组。这些患者的年龄在30岁到85岁之间，并且都患有超重或肥胖。主要复合终点是低氧血症（家庭血氧饱和度≤93%）、急诊就诊、住院或死亡。所有分析均使用同时进行随机化的对照，并针对 SARS-CoV-2 疫苗接种和接受其他试验药物进行了调整。接种 CoV-2 疫苗并接受其他试验药物。共有 1431 名患者接受了随机分组；其中 1323 名患者被纳入初步分析。患者的中位年龄为 46 岁； 56% 为女性（其中 6% 已怀孕），52% 已接种疫苗。二甲双胍的主要事件调整后比值比为 0.84（95% CI，0.66 至 1.09；P = 0.19），伊维菌素为 1.05（95% CI，0.76 至 1.45；P = 0.78），伊维菌素为 0.94（95% CI，0.66 至 1.36；P = 0.78）。 0.75）与氟伏沙明。在预先指定的二次分析中，二甲双胍的急诊就诊、住院或死亡的调整比值比为 0.58（95% CI，0.35 至 0.94），伊维菌素为 1.39（95% CI，0.72 至 2.69），氟伏沙明为 1.17（95% CI，0.57 至 2.40）。二甲双胍住院或死亡的调整后比值比为 0.47（95% CI，0.20 至 1.11），伊维菌素为 0.73（95% CI，0.19 至 2.77），氟伏沙明为 1.11（95% CI，0.33 至 3.76）。所评估的三种药物均无法预防与 Covid-19 相关的低氧血症、急诊就诊、住院或死亡的发生。 （由 Parsemus 基金会和其他机构资助；COVID-OUT ClinicalTrials.gov 编号，NCT04510194。）
Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs — metformin, ivermectin, and fluvoxamine — in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. CoV-2 vaccination and receipt of other trial medications. A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.)